The family of antibacterial and antitumor agents, known collectively as the LL-E33288 complex, are described and claimed in a series of related, commonly assigned U. S. patent applications, namely Ser. No. 672,031, filed Nov. 16, 1984 (now abandoned); Ser. No. 787,066, filed Oct. 17, 1985; and Ser. No. 9,321, filed Jan. 30, 1987.
These applications describe the LL-E33288 complex, the components thereof, namely LL-E33288.alpha..sub.1 -Br, LL-E33288.alpha..sub.1 -I, LL-E33288.alpha..sub.2 -I, LL-E33288.alpha..sub.2 -I, LL-E33288.alpha..sub.3 -Br, LL-E33288.alpha..sub.3 -I, LL-E33288.alpha..sub.4 -Br, LL-E33288.beta..sub.1 -Br, LL-E33288.beta..sub.1 -I, LL-E33288.beta..sub.2 -Br, LL-E33288.beta..sub.2 -I, LL-E33288.gamma..sub.1 -Br, LL-E33288.gamma..sub.1 -I, and LL-E33288.delta..sub.1 -I, and methods for their production by aerobic fermentation utilizing a new strain of Micromonospora echinospora ssp calichensis or natural or derived mutants thereof.
The antibacterial and antitumor agents LL-E33288.epsilon.-I and LL-E33288.epsilon.-Br, which are the subject of commonly assigned, copending Ser. No. 07/161,627, filed Feb. 29, 1988, are produced by the same microorganisms under same fermentation conditions. Ser. No. 07/161,627 describes methods for the production of LL-E33288.epsilon.-I and LL-E33288.epsilon.-Br as well as establishing their antibacterial and antitumor activity characterizing the products by physical and chemical data and disclosing a proposed structure.
Certain other antibiotics are pertinent to this invention, namely:
(1) Esperamicin BBM-1675, a novel class of potent antitumor antibiotics I. Physico-chemical data and partial structure. M. Konishi, et al., J. Antibiotics, 38, 1605 (1985). A new antitumor antibiotic comples. M. Konishi, et al., UK patent application GB No. 2,141,425A, May 15, 1985.
(2) New antitumor antibiotics, FR-900405 and FR-900406. I. Taxonomy of the producing strain. M. Iwami, et al., J. Antibiotics, 38, 835 (1985). New antitumor antibiotics FR-900405 and FR-900406. II. Production, isolation, characterization and antitumor activity. S. Kiyoto, et al., J. Antibiotics, 38, 840 (1985).
(3) PD 114759 and PD 115028, novel antitumor antibiotics with phenomenal potency. I Isolation and characterization. R. R. Bunge, et al., J. Antibiotics, 37, 1566 (1984). Biological and biochemical activities of the novel antitumor antibiotic PD 114759 and related derivatives. D. W. Fry, et al., Investigational New Drugs, 4, 3 (1986).
(4) New antibiotic complex CL-1577A and CL-1577B produced by Streptomyces sp. ATCC 39363. European Patent application No. 0,132,082,A2.
(5) CL-1577D and CL-1577E Antibiotic antitumor compounds, their production and use. U.S. Pat. No. 4,539,203.
(6) CL-1724 Antibiotic compounds, their production and use. U.S. Pat. No. 4,554,162.